The Coming of Age in Iodane‐Guided ortho‐C−H Propargylation: From Insight to Synthetic Potential

Abstract

As early as 1991 Ochiai et al. reported that an acid-activated form of phenyliodine diacetate, PhI(OAc) , undergoes a reaction with propargyl-silanes, germanes and stannanes to give the ortho-propargyl iodobenzene. This formal C-H alkylation was proposed to take place through an unusual (even to date) iodonio-based [3,3] rearrangement of an intermediate allenylsilane. Although this mechanistic principle has been invoked in related iodane-directed C-H coupling reaction, some underlying principles have remained unaddressed, and the reaction rarely employed. Herein, DFT evidence for a mechanism best described as iodine-guided electrophilic aromatic substitution is presented. Using a newly optimized reaction protocol that significantly reduces the undesired reduction process, the potency of the method is showcased through the synthesis of >40 structurally diverse ortho-iodo propargyl (or allenyl) arenes.

The ortho‐Difluoroalkylation of Aryliodanes with Enol Silyl Ethers: Rearrangement Enabled by a Fluorine Effect

“…Recently, Shafir et al. reported an unconventional Claisen rearrangement in their study of ortho ‐propagylation of bis(acyloxy)iodoarenes, encouraging us to reexamine the present rearrangement. IM3 has the C−I bond length equal to that (2.09 Å) in IM1 and two distant OTf − groups, suggesting that IM3 had better be represented by the resonance structure IM3 RE1 with iodine(I) rather than IM3 RE2 with iodine(III).…”

para‐Selective Benzylation of Aryl Iodides by the in situ Preparation of ArIF2: a Hypervalent Iodine‐Guided Electrophilic Substitution

“…The recent and rapid development of hypervalent iodine‐guided electrophilic substitutions (Scheme ) began from a series of papers by Khatri and Zhu in which they rediscovered and evaluated of the reductive iodonio‐Claisen rearrangement (RICR) RICR‐type reactions have undergone review by Shafir and also in a section of a review on C–C bond forming reactions by Hyatt et al in 2019 …”

Dearomative Dual Functionalization of Aryl Iodanes

“…To verify our hypothesis, we first needed to identify the first nucleophile (Nu 1 ) to be used for [3,3] sigmatropic rearrangement of the aryl iodane (Scheme e). A variety of nucleophiles, including allyl/propargyl silanes,– β‐dicarbonyl compounds, 2‐naphthols, difluoroenol silyl ethers, and α‐stannyl nitriles, were found to be suitable for the rearrangement of aryl iodanes. However, the selection of nucleophiles for dearomative rearrangement must meet the following criteria: 1) The rearrangement of aryl iodanes with the nucleophile must take place at low temperature and be complete in a short time so as to avoid the deterioration of the in situ generated dearomative intermediate I , which is likely to be unstable in view of its dearomatized structure with a pendant iodine(III) moiety; 2) the nucleophile must be highly reactive towards aryl iodanes in the rearrangement stage, but completely inactive towards the highly electrophilic dearomative intermediate I so that I can be trapped by the second nucleophile (Nu 2 ; Scheme e); 3) the nucleophile should be a versatile building block to ensure the synthetic utility of the final dearomatization product.…”